Characteristics and Outcomes of Lung-RADS Version 2022 Atypical Pulmonary Cysts With Ground-Glass Components on Lung Cancer Screening CT: Secondary Analysis of BioMILD Trial Data

Lung-RADS version 2022 (v2022) introduced the atypical pulmonary cyst, defined on lung cancer screening (LCS) CT as a unilocular thick-walled (any wall thickening ≥ 2 mm) or multilocular cyst [1]. Lung-RADS v2022 categorizes atypical pulmonary cysts at baseline detection as category 4A and recommends management with a 3-month follow-up low-dose CT examination, regardless of atypical pulmonary cyst density (noting that PET/CT may also be considered in the presence of a solid component measuring ≥ 8 mm) [1]. Accordingly, atypical pulmonary cysts with a ground-glass component require initial close surveillance, which contrasts with management of other ground-glass nodules, which generally are considered indolent. For example, Lung-RADS v2022 recommends 12-month follow-up for ground-glass nodules measuring less than 30 mm that are detected at baseline. Nonetheless, limited data address atypical pulmonary cysts with ground-glass components. This study evaluated the characteristics and outcomes of Lung-RADS v2022 atypical pulmonary cysts with ground-glass components detected on LCS CT. The retrospective study entailed a secondary analysis of data from the BioMILD (Bio Multicentric Italian Lung Detection) trial [2]. That prospective single-center trial enrolled 4119 former smokers or smokers 50–75 years old who met predefined risk-factor criteria between January 2013 and March 2016. Participants underwent baseline and follow-up rounds of low-dose LCS CT, which continued after completion of the trial enrollment period. Each examination was interpreted in consensus by two thoracic radiologists (among 10 total participating radiologists), who recorded nodule characteristics using a structured electronic form. The institutional review board approved the study. Participants provided written informed consent, which allowed use of trial data for future retrospective analyses. The BioMILD dataset was queried on December 1, 2024, for the terms “bulla”, “cyst”, “bubblelike lucencies”, “cavitation”, or “emphysema”. Two radiologists (M.B. and M.R., with 4 and 7 years of posttraining experience in LCS, respectively) reviewed the search results in consensus to identify nodules meeting Lung-RADS v2022 criteria for atypical pulmonary cysts that also contained a ground-glass component. These two radiologists evaluated LCS examinations in consensus for atypical pulmonary cyst characteristics at detection and assessed follow-up examinations for increases in atypical pulmonary cyst size and/or density. Patient-level outcomes were recorded in terms of lung cancer (LC) diagnoses and deaths due to any cause. The Supplemental Methods provide additional details. The final study sample included 24 (13 men and 11 women; median age, 60.5 years) of 4119 participants (0.6%) with 29 atypical pulmonary cysts with ground-glass components. Table 1 summarizes patient and atypical pulmonary cyst characteristics. Of 29 atypical pulmonary cysts, 20 were identified on a baseline LCS round, and nine were identified on a follow-up round (including six that developed from a noncystic pure ground-glass nodule and three that developed from a thin-walled cyst)